1. PI and Coordinator Webinar
June 26, 2018

2. Enrollment 121 patients consented 50 eligible for randomization (40%)
34 randomized
Randomization by month:
Mar: 2
Apr: 8
May: 11
June (so far) 13

3. Site Readiness 87 Sites have submitted to the CIRB
77 Sites CIRB Approved
65 readiness calls completed
62 are released to enroll
38 sites have enrolled at least one subject

4. Site Readiness (cont) VA site update:
All 7 VA sites have been actively completing their regulatory documents.
Waiting to receive an updated Data Use Agreement from VA
Have sent a request to proceed with submissions while this is pending
MUSC will be scheduling a separate WebDCU training for VA coordinators

5. Site Readiness (cont) New ARCADIA Sites:
Sites are now posted in WebDCU so DOAs can be created and documents loaded
We will spend the last portion of the Webinar in July training the new site coordinators on webdcu.
All new sites received their reg. submission packets on May 21st.
Shout out to University Hospital Cleveland and Houston Methodist for their eagerness to start—they are almost ready to submit to the CIRB!

6. Top enrolling sites Site Consented Randomized
United Hospital, St. Paul 10 3
University of Cincinnati 8
Oregon Health and Sciences
Intercoastal Medical Group 6 2
Memorial Herman
UF Health Shands 5
Harborview Medical Center
UPMC 1

7. Top enrolling sites Site Consented Randomized Los Angeles County + USC4
NYP Columbia 2
Northwestern Memorial
University of Iowa 1
NYP Weill Cornell

8. Protocol trial agreements
Year 2 CTAs have been sent out to 111 sites (except 3 new ones)
48 year 2 CTAs returned
Site PI should encourage their contracts team to sign and return.
Identify responsible parties
Check in with them regularly
This makes a big difference
Seek support from institutional/departmental leadership
We are happy to help however we can!

9. ARCADIA Newsletter First issue June 12, 2018
Includes discussion of NAVIGATE ESUS results as pertains to ARCADIA
Please review these newsletters
There will be important updates and information
Please send suggestions/ideas for things you would like to hear about.

10. Regulatory updates/reminders
ICF version 5- addition of the 30-Day follow-up phone calls after randomization and at the end of the study.
These changes are being made administratively by the CIRB. When they are sent to your site they are approved and should be used. They do not require approval of your local IRB. You should not be using version 4, once you receive version 5.0
Site Names-should be consistent on all submission documents and should include where the subject will be consented and where follow-up will occur.

11. Regulatory updates/reminders
HIPAA Waiver to screen subjects-rationale for this
Changes on the DOA require an Administrative Amendment
Putting any end date for a team member will remove them from the DOA
If a subject stops taking study medication this does not automatically mean they are withdrawing from the study. We want to continue to follow subjects unless they officially withdraw.
Webinar to discuss the changes in regulatory submission process and WebDCU™ updates to be held July 26th 2-3pm ET

12. Project Tools
Physician Letter- Be sure to send this to the subject’s PCP
Important for retention
Avoid subject being prescribed prohibited medications
Better care and follow-up for subjects
Document that letter was sent or save a copy in the subject
research record

14. POINT trial
Double-blinded randomized trial of aspirin vs. aspirin/clopidogrel
4,881 subjects enrolled at 269 sites in 10 countries:
Minor stroke (NIHSS ≤3) or high-risk TIA (ABDC2 score ≥4) in prior 12 hours
Excluded if thrombolysis/thrombectomy, anticoagulation, carotid surgery
Required testing:
Echo, 20 hours of heart-rhythm monitoring, extracranial vessel imaging
Treatment arm 1: Aspirin ( mg daily) + placebo
Treatment arm 2: Aspirin + clopidogrel (600-mg load + 75 mg daily)
Johnston SC et al. NEJM May 16, 2018

15. POINT trial: Discussion relevant to ARCADIA
POINT does not apply to everyone, trial limited to those with:
Minor stroke (NIHSS ≤3), High-risk TIA (ABDC2 score ≥4) in prior 12 hours
Those who did not undergo thrombolysis/thrombectomy
Optimal benefit appears to occur during the first 7 days:
Reduction in risk of early ischemic events up to 7 or 30 days after stroke
Increase in risk of major hemorrhage at days 8-90 days
DAPT decision is up to the local investigator/clinical care team
ARCADIA does not dictate clinical care prior to randomization
Once patient randomized, then they cannot take ANY non-study aspirin, clopidogrel, or other anti-thrombotic
Suggest delaying randomization until PI comfortable with single anti-platelet

16. Reminder: Introduction of reversal agent (Andexanet alfa (trade name AndexXa))

17. Lab Core Update Shipment Attachment submissions
Review shipment before sending
BioBank and subject consent
Drawing blood sample from venipuncture vs an indwelling line (IV):
Withdraw and discard the dead space volume in the line before drawing the sample;
Confirm that there is no second line upstream of the draw line being infused with anything.

18. Echo Core Update
Remember to send your site’s first echo to the Echo Core Lab
Subsequent echos will be sent twice annually
De-identified echos are best, but not required
Check with echo lab to see if they can de-identify for you
Echos are videos and typically do not use the standard neuroimaging data management tools like DICOM
It is unlikely you will be able to de-identify these yourself
If unable to de-identify it is ok to send the echo anyway; Columbia is study sponsor and echo core, and has permission to get data
Data will be stored in secure fashion

19. EKG Core Update
Remember to de-identify/redact EKGs before sending to EKG Core
Use the first EKG after stroke, when available
Do not send multiple EKGs on patients

20. Identifying eligible patients
Experience at United from St. Paul…

21. FAQs (continued)
Q= Does hemorrhagic transformation exclude a subject from ARCADIA? A= No, hemorrhagic transformation does not exclude a patient. But remember that hemorrhagic transformation comes in different flavors: petechial, small/large, asymptomatic/symptomatic. Petechial hemorrhage seen by MRI is very common (60-70% depending on MR technique). In presence of hemorrhage, wait 14 days from time of stroke to randomize and re-evaluate the subject eligibility status to ensure they still meet criteria. In general, PI should decide when the patient can be randomized; in some cases, you may want to wait more than 14 days. If hemorrhage identified several days/weeks after initial stroke, reasonable to wait for 14 days after hemorrhage identified. Enroll early and randomize late

22. FAQs (Continued)
Q= A patient has a left MCA infarction. There is a 90% right ICA stenosis. Can the patient be enrolled?
A=  Yes. The determination of whether a patient is eligible for consent/enrolment is based on the PI’s determination of the patient having an embolic stroke of undetermined source (ESUS). It is not based on the presence of 50% or more stenosis in a vessel if that vessel cannot be considered a cause of their stroke.

23. FAQs (Continued)
Q = My patient is 48 years old and had a right parietal infarction. He was found to also have a PFO. Is he eligible?
A = Yes. Patients with PFO are eligible for consent/enrolment. If the patient is going to have the PFO closed, this should be done first and the patient consented afterwards, when they are almost ready to be randomized, if eligible. Most interventional cardiologists will want patients to take aspirin/clopidogrel for 90 days after a PFO is closed, so this would delay their eligibility for the study. It may be possible to discuss with the cardiologist whether the duration of dual antiplatelet therapy can be shortened if the patient turns out to be eligible for randomization, so as to stay within the 120 day randomization window.

24. FAQs (Continued)
Q = My patient may be discharged to inpatient rehab or a SNF, when can randomization occur?
A = May depend on when eligible. If able to randomize while still in hospital, may be able to send study meds for admin to next location. If can’t randomize until after discharge, may want to coordinate with next location about dispensing medications. Also, if reasonable, can also wait until discharged from inpatient rehab or SNF if short term stay.
What have folks done to deal with this?

25. Determining eligibility for consent
Can consent as soon as standard-of-care tests are completed
As early as 24 hours after admission after echo, ECG, imaging, telemetry, etc
Standard-of-care tests must be from after stroke onset
But please let us know if there is an otherwise eligible patient who doesn’t have this (e.g., had a recent echo or vascular imaging and team does not want to repeat)
Miscellaneous
Hemorrhagic conversion is NOT an exclusion (though would delay timing of randomization)
Large-vessel occlusion is NOT an exclusion if it is not atherosclerotic

26. Maintaining confidentiality
Remove ALL identifiers (name, DOB, MRN, etc) from ECGs and safety packets before uploading to WebDCU.
If you are unsure if something is an identifier (e.g. “Account Number”) go ahead and remove it.
Identifiers are sometimes still visible when manually removed. Preferred de- identification method is electronic removal using Adobe Acrobat or other PDF editor

27. Consent process
LAR is appropriate ONLY when a subject is incapable of giving informed consent (e.g. due to neurological deficit)
When subject is capable of giving consent, but is unable to physically sign the consent:
- Impartial witness should be present during consent process and sign consent document
- If possible, subject should ‘make their mark’ on signature lines

28. Hotline 24-hour telephone hotline
Please use it for any urgent questions
Eligibility, randomization, unblinding, etc
( AR-CADI): useful to save in your cell phone
The hotline automatically calls all four PIs
Please let it ring
And call back if no luck—one of us will pick up!

29. Next webinar: July 24 at 2 PM ET
Next steps
Please complete trial agreements and CIRB submissions
Actively screen
Send us feedback—we will make changes as needed to make this trial successful!
Next webinar: July 24 at 2 PM ET
HAVE A GREAT SUMMER!